Exploring phenotype and recovery from relapses in relapsing-remitting multiple sclerosis patients: old versus new Disease-Modifying Therapies

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Introduction and aims
The clinical course of relapsing remitting multiple sclerosis (RRMS) is largely determined by the frequency, severity, and recovery of relapses, which show extreme variability during the disease course.
A high frequency and severity of relapses, particularly in the first 2 years, have been described as strong predictors of greater disease burden in terms of disability accumulation and treatment failure(s).
The relapse phenotype has not been fully investigated and it has not been included as a parameter in clinical trials to verify a disease modifying therapy (DMT) and scarce data with controversial results are available from small studies
The incomplete recovery, defined by the persistence of neurologic deficits after a relapse, has been observed in 34–59% of relapses.
The disease characteristics that could be associated to the degree of recovery have only been found in few real-world studies and cannot be generalized.
Notably, the degree of recovery from the first relapse in a patient’s course was shown to predict the time to disability progression and the time to transition into secondary progressive MS, although the association of each relapse phenotype to the degree of recovery has not been characterized unequivocally.
The primary study outcome was the evaluation of first relapse phenotype in RRMS patients generally and based on the first-line DMT prescribed during the first 5 years of treatment. Next, incomplete recovery (sequalae) based on relapse phenotype and the type of first-line DMT was determined.
Ancillary, the role of each relapse phenotype on the probability to obtain an EDSS score ≥ 4.0 during the entire follow-up period (the first 5 years of therapy unless the DMT was discontinued earlier) was investigated.

Results
All the 2,676 patients fulfilled the required criteria. The first-relapse phenotype of 712 relapses was determined. Being female and higher number of relapses before diagnosis were associated with higher risk of relapse in the 5-year period (HR = 1.3, 95%CI 1.07–1.46; p = 0.005 and HR = 1.1, 95%CI 1.06–1.15; p < 0.001, respectively) whilst older age at the time of first DMT prescribed (HR = 0.98, 95% CI 0.98–0.99; p < 0.001) to a lower risk. The pyramidal phenotype was associated with higher age and baseline EDSS score. Older age correlated also with worse sequelae (proportional OR = 1.02, 95%CI 1.01–1.04; p = 0.004), as the occurrence of a second relapse before the DMT starting (proportional OR = 1.72, 95%CI 1.01–2.92; p = 0.044). The pyramidal phenotype, adjusted for age and other phenotypes was associated to a 1.95-fold higher risk of severe or moderate sequelae (proportional OR = 1.95 95%CI 1.35–2.80; p < 0.001).

Conclusions
The characterization of different relapse phenotypes from early phases of RRMS and the first DMT prescribed should be considered a determinant of therapeutic choice.


Pubblicazioni e Comunicazioni a Congressi/ Publications and Congress Presentations
First relapse phenotype and recovery in naïve relapsing remitting multiple sclerosis patients undergoing first-line therapies: an Italian Registry study. Submitted to European Journal of Neurology as original paper

First relapse phenotype and recovery in naïve relapsing remitting multiple sclerosis patients undergoing first-line therapies: an Italian Registry study. Submitted to EAN 2022 as poster

First relapse phenotype and recovery in naïve relapsing remitting multiple sclerosis patients undergoing first-line therapies: an Italian Registry study. Presented as poster to ECTRIMS 2021 and accepted as a poster for the next AAN congress 2022

Zanghì A, et al. First-line therapies in late-onset multiple sclerosis: An Italian registry study. Eur J Neurol. 2021 Dec;28(12):4117-4123. doi: 10.1111/ene.15006